Niu Jian, Wang Yue, Wang Ji, Bin Liu, Hu Xin
General Surgery of the Hospital Affiliated Hospital of Xuzhou Medical University, Digestive Disease Research Laboratory of Xuzhou Medical University, Xuzhou, Jiangsu 221002, PR China.
The University of Texas Graduate School of Biomedical Sciences at Houston, MD Anderson Cancer Center, Houston, TX 77030, USA.
Aging (Albany NY). 2016 Dec 28;8(12):3520-3534. doi: 10.18632/aging.101146.
One important process in liver cancer growth and progression is angiogenesis. Vascular endothelial growth factor (VEGF) has the significant role in liver cancer angiogenesis. sFlt1 (soluble Fms-like tyrosine kinase-1) is the promising inhibitor of VEGF and can be used as the new method of inhibiting angiogenesis. MSCs (Mesenchymal stem cells) can infiltrate into tumor tissue and function as the efficient transgene delivery mediator. Here, we engineered murine MSCs to express sFlt1 and examined the anti-tumor effect of MSC- sFlt1 in combination with continues low-dose doxorubicin treatment. We found that this combination therapy significantly inhibited liver cancer cells proliferation. Above all, HepG2 xenografts treated with this combination therapy went into remission. It is of note that this inhibition effect was not p53 binding and by increasing caspase8. This study suggests that this combination treatment has novel therapeutic potential for liver cancer because of significantly inhibiting cancer cells growth and anti-angiogenesis in vitro and in vivo.
血管生成是肝癌生长和进展过程中的一个重要过程。血管内皮生长因子（VEGF）在肝癌血管生成中发挥着重要作用。可溶性Fms样酪氨酸激酶-1（sFlt1）是一种很有前景的VEGF抑制剂，可作为抑制血管生成的新方法。间充质干细胞（MSCs）能够浸润到肿瘤组织中，并作为有效的转基因传递介质发挥作用。在此，我们对小鼠间充质干细胞进行基因改造使其表达sFlt1，并研究了MSC-sFlt1与持续低剂量阿霉素联合治疗的抗肿瘤效果。我们发现这种联合治疗显著抑制了肝癌细胞的增殖。最重要的是，接受这种联合治疗的HepG2异种移植瘤进入缓解期。值得注意的是，这种抑制作用并非通过p53结合和增加半胱天冬酶8来实现。这项研究表明，这种联合治疗由于在体外和体内均能显著抑制癌细胞生长和抗血管生成，因而对肝癌具有新的治疗潜力。
